Human Mesenchymal Stem Cells Genetically Engineered to Overexpress Brain-derived Neurotrophic Factor Improve Outcomes in Huntington’s Disease Mouse Models

Human Mesenchymal Stem Cells Genetically Engineered to Overexpress Brain-derived Neurotrophic Factor Improve Outcomes in Huntington's Disease Mouse Models

Molecular Therapy 24, 965 (May 2016). doi:10.1038/mt.2016.12

Authors: Kari Pollock, Heather Dahlenburg, Haley Nelson, Kyle D Fink, Whitney Cary, Kyle Hendrix, Geralyn Annett, Audrey Torrest, Peter Deng, Joshua Gutierrez, Catherine Nacey, Karen Pepper, Stefanos Kalomoiris, Johnathon D Anderson, Jeannine McGee, William Gruenloh, Brian Fury, Gerhard Bauer, Alexandria Duffy, Theresa Tempkin, Vicki Wheelock & Jan A Nolta

from Cancer via ola Kala on Inoreader http://ift.tt/256WyUV
via IFTTT

In This Issue

In This Issue

Molecular Therapy 24, 847 (May 2016). doi:10.1038/mt.2016.73

from Cancer via ola Kala on Inoreader http://ift.tt/1XFRJj3
via IFTTT

Inhibiting Notch Activity in Breast Cancer Stem Cells by Glucose Functionalized Nanoparticles Carrying γ-secretase Inhibitors

Inhibiting Notch Activity in Breast Cancer Stem Cells by Glucose Functionalized Nanoparticles Carrying γ-secretase Inhibitors

Molecular Therapy 24, 926 (May 2016). doi:10.1038/mt.2016.42

Authors: Veronika Mamaeva, Rasmus Niemi, Michaela Beck, Ezgi Özliseli, Diti Desai, Sebastian Landor, Tove Gronroos, Pauliina Kronqvist, Ina K N Pettersen, Emmet McCormack, Jessica M Rosenholm, Mika Linden & Cecilia Sahlgren

from Cancer via ola Kala on Inoreader http://ift.tt/256W4xZ
via IFTTT

Research Highlights

Research Highlights

Molecular Therapy 24, 848 (May 2016). doi:10.1038/mt.2016.74

Author:

from Cancer via ola Kala on Inoreader http://ift.tt/1XFS3OZ
via IFTTT

Overcoming Challenges in CAR T-cell Product CGMP Release

Overcoming Challenges in CAR T-cell Product CGMP Release

Molecular Therapy 24, 845 (May 2016). doi:10.1038/mt.2016.72

Authors: Concetta Quintarelli, Franco Locatelli, Ignazio Caruana & Biagio De Angelis

from Cancer via ola Kala on Inoreader http://ift.tt/256Wm7Y
via IFTTT

Multistage Delivery Technologies: Multifunctional, Interdisciplinary Approaches to Nanomedicine

Multistage Delivery Technologies: Multifunctional, Interdisciplinary Approaches to Nanomedicine

Molecular Therapy 24, 849 (May 2016). doi:10.1038/mt.2016.75

Authors: Matthew T Haynes & Leaf Huang

from Cancer via ola Kala on Inoreader http://ift.tt/1XFS19R
via IFTTT

Argonaute 2-dependent Regulation of Gene Expression by Single-stranded miRNA Mimics

Argonaute 2-dependent Regulation of Gene Expression by Single-stranded miRNA Mimics

Molecular Therapy 24, 946 (May 2016). doi:10.1038/mt.2016.39

Authors: Masayuki Matsui, Thazha P Prakash & David R Corey

from Cancer via ola Kala on Inoreader http://ift.tt/256Wk05
via IFTTT

Endogenous Transposase Source in Human Cells Mobilizes piggyBac Transposons

Endogenous Transposase Source in Human Cells Mobilizes piggyBac Transposons

Molecular Therapy 24, 851 (May 2016). doi:10.1038/mt.2016.76

Author: Zoltán Ivics

from Cancer via ola Kala on Inoreader http://ift.tt/1XFS6u7
via IFTTT

H7N9 Live Attenuated Influenza Vaccine Is Highly Immunogenic, Prevents Virus Replication, and Protects Against Severe Bronchopneumonia in Ferrets

H7N9 Live Attenuated Influenza Vaccine Is Highly Immunogenic, Prevents Virus Replication, and Protects Against Severe Bronchopneumonia in Ferrets

Molecular Therapy 24, 991 (May 2016). doi:10.1038/mt.2016.23

Authors: Jørgen de Jonge, Irina Isakova-Sivak, Harry van Dijken, Sanne Spijkers, Justin Mouthaan, Rineke de Jong, Tatiana Smolonogina, Paul Roholl & Larisa Rudenko

from Cancer via ola Kala on Inoreader http://ift.tt/256WF2A
via IFTTT

Rescue of a Mouse Model of Spinal Muscular Atrophy With Respiratory Distress Type 1 by AAV9-IGHMBP2 Is Dose Dependent

Rescue of a Mouse Model of Spinal Muscular Atrophy With Respiratory Distress Type 1 by AAV9-IGHMBP2 Is Dose Dependent

Molecular Therapy 24, 855 (May 2016). doi:10.1038/mt.2016.33

Authors: Monir Shababi, Zhihua Feng, Eric Villalon, Christine M Sibigtroth, Erkan Y Osman, Madeline R Miller, Patricka A Williams-Simon, Abby Lombardi, Thalia H Sass, Arleigh K Atkinson, Michael L Garcia, Chien-Ping Ko & Christian L Lorson

from Cancer via ola Kala on Inoreader http://ift.tt/1XFRWmA
via IFTTT

Chop Deficiency Protects Mice Against Bleomycin-induced Pulmonary Fibrosis by Attenuating M2 Macrophage Production

Chop Deficiency Protects Mice Against Bleomycin-induced Pulmonary Fibrosis by Attenuating M2 Macrophage Production

Molecular Therapy 24, 915 (May 2016). doi:10.1038/mt.2016.36

Authors: Yingying Yao, Yi Wang, Zhijun Zhang, Long He, Jianghui Zhu, Meng Zhang, Xiaoyu He, Zhenshun Cheng, Qilin Ao, Yong Cao, Ping Yang, Yunchao Su, Jianping Zhao, Shu Zhang, Qilin Yu, Qin Ning, Xudong Xiang, Weining Xiong, Cong-Yi Wang & Yongjian Xu

from Cancer via ola Kala on Inoreader http://ift.tt/256W3Kr
via IFTTT

AAV-mediated Gene Therapy Halts Retinal Degeneration in PDE6β-deficient Dogs

AAV-mediated Gene Therapy Halts Retinal Degeneration in PDE6β-deficient Dogs

Molecular Therapy 24, 867 (May 2016). doi:10.1038/mt.2016.37

Authors: Virginie Pichard, Nathalie Provost, Alexandra Mendes-Madeira, Lyse Libeau, Philippe Hulin, Kizito-Tshitoko Tshilenge, Marine Biget, Baptiste Ameline, Jack-Yves Deschamps, Michel Weber, Guylène Le Meur, Marie-Anne Colle, Philippe Moullier & Fabienne Rolling

from Cancer via ola Kala on Inoreader http://ift.tt/1XFRZyG
via IFTTT

MiR-298 Counteracts Mutant Androgen Receptor Toxicity in Spinal and Bulbar Muscular Atrophy

MiR-298 Counteracts Mutant Androgen Receptor Toxicity in Spinal and Bulbar Muscular Atrophy

Molecular Therapy 24, 937 (May 2016). doi:10.1038/mt.2016.13

Authors: Naemeh Pourshafie, Philip R Lee, Ke-lian Chen, George G Harmison, Laura C Bott, Masahisa Katsuno, Gen Sobue, Barrington G Burnett, Kenneth H Fischbeck & Carlo Rinaldi

from Cancer via ola Kala on Inoreader http://ift.tt/256W4ht
via IFTTT

Gene Transfer of Brain-derived Neurotrophic Factor (BDNF) Prevents Neurodegeneration Triggered by FXN Deficiency

Gene Transfer of Brain-derived Neurotrophic Factor (BDNF) Prevents Neurodegeneration Triggered by FXN Deficiency

Molecular Therapy 24, 877 (May 2016). doi:10.1038/mt.2016.32

Authors: Yurika Katsu-Jiménez, Frida Loría, Juan Carlos Corona & Javier Díaz-Nido

from Cancer via ola Kala on Inoreader http://ift.tt/1XFRXqs
via IFTTT

Induced Apoptosis Investigation in Wild-type and FLT3-ITD Acute Myeloid Leukemia Cells by Nanochannel Electroporation and Single-cell qRT-PCR

Induced Apoptosis Investigation in Wild-type and FLT3-ITD Acute Myeloid Leukemia Cells by Nanochannel Electroporation and Single-cell qRT-PCR

Molecular Therapy 24, 956 (May 2016). doi:10.1038/mt.2016.6

Authors: Keliang Gao, Xiaomeng Huang, Chi-Ling Chiang, Xinmei Wang, Lingqian Chang, Pouyan Boukany, Guido Marcucci, Robert Lee & Ly James Lee

from Cancer via ola Kala on Inoreader http://ift.tt/256WqEL
via IFTTT

Development and Validation of a Small Single-domain Antibody That Effectively Inhibits Matrix Metalloproteinase 8

Development and Validation of a Small Single-domain Antibody That Effectively Inhibits Matrix Metalloproteinase 8

Molecular Therapy 24, 890 (May 2016). doi:10.1038/mt.2016.2

Authors: Delphine Demeestere, Eline Dejonckheere, Sophie Steeland, Paco Hulpiau, Jurgen Haustraete, Nick Devoogdt, Rielana Wichert, Christoph Becker-Pauly, Elien Van Wonterghem, Sylviane Dewaele, Griet Van Imschoot, Jeroen Aerts, Lutgarde Arckens, Yvan Saeys, Claude Libert & Roosmarijn E Vandenbroucke

from Cancer via ola Kala on Inoreader http://ift.tt/1XFRZP7
via IFTTT

A Role for the Long Noncoding RNA SENCR in Commitment and Function of Endothelial Cells

A Role for the Long Noncoding RNA SENCR in Commitment and Function of Endothelial Cells

Molecular Therapy 24, 978 (May 2016). doi:10.1038/mt.2016.41

Authors: Mounia Boulberdaa, Elizabeth Scott, Margaret Ballantyne, Raquel Garcia, Betty Descamps, Gianni D Angelini, Mairi Brittan, Amanda Hunter, Martin McBride, John McClure, Joseph M Miano, Costanza Emanueli, Nicholas L Mills, Joanne C Mountford & Andrew H Baker

from Cancer via ola Kala on Inoreader http://ift.tt/256WgNM
via IFTTT

SSRP1 Contributes to the Malignancy of Hepatocellular Carcinoma and Is Negatively Regulated by miR-497

SSRP1 Contributes to the Malignancy of Hepatocellular Carcinoma and Is Negatively Regulated by miR-497

Molecular Therapy 24, 903 (May 2016). doi:10.1038/mt.2016.9

Authors: Qianshan Ding, Ke He, Tao Luo, Yunchao Deng, Hanning Wang, Hao Liu, Jinqian Zhang, Kaiyun Chen, Jinfeng Xiao, Xiaopeng Duan, Rui Huang, Zhenglin Xia, Wenjie Zhou, Jinliang He, Honggang Yu, Xingyuan Jiao & Guoan Xiang

from Cancer via ola Kala on Inoreader http://ift.tt/256Wnsx
via IFTTT

Development of an Interleukin-1β Vaccine in Patients with Type 2 Diabetes

Development of an Interleukin-1β Vaccine in Patients with Type 2 Diabetes

Molecular Therapy 24, 1003 (May 2016). doi:10.1038/mt.2015.227

Authors: Claudia Cavelti-Weder, Katharina Timper, Eleonora Seelig, Cornelia Keller, Martin Osranek, Ute Lässing, Gunther Spohn, Patrik Maurer, Philipp Müller, Gary T Jennings, Joerg Willers, Philippe Saudan, Marc Y Donath & Martin F Bachmann

from Cancer via ola Kala on Inoreader http://ift.tt/1sHXIbU
via IFTTT

Up-regulation of long non-coding RNA PANDAR is associated with poor prognosis and promotes tumorigenesis in bladder cancer

Long non-coding RNAs (lncRNAs) have emerged as biomarkers and important regulators of tumor development and progression. PANDAR (promoter of CDKN1A antisense DNA damage activated RNA) is a novel long non-codin...

from Cancer via ola Kala on Inoreader http://ift.tt/256V8d5
via IFTTT

Repeated biopsy results

from Cancer via ola Kala on Inoreader http://ift.tt/1NCP5si
via IFTTT

Minimally invasive surgery for stomach cancer

Laparoscopic surgery for gastric cancer has become extremely widespread in recent years especially in Asian countries due to its low invasiveness. As to evidence of indication for laparoscopic surgery for gastric cancer, laparoscopic surgery for gastric cancer often appears to be indicated for early gastric cancer at many institutions, while evidence was considered to be insufficient to recommend laparoscopic surgery for gastric cancer at Stage II and above. There are also problems with indications for cases other than tumour factors. No meta-analyses and prospective studies have been reported, but outcomes of laparoscopic surgery for gastric cancer in gastric cancer patients with co-morbid and/or existing diseases have been reported in retrospective studies. Indications in the elderly appear to be favourable in terms of post-operative ambulation considering factors such as the degree of dissection in accordance with the status of the patient. Meta-analyses, randomized controlled trials and several retrospective studies have compared the short-term usefulness of laparoscopic surgery for gastric cancer with that of conventional gastrectomy. The superiority of laparoscopic surgery for gastric cancer has been reported in terms of the reduced amount of bleeding, a reduction in the administration frequency and period of analgesic doses, a reduction in the duration of fever, early recovery of intestinal movement and early return to oral intake. A small-scale randomized controlled trial and several retrospective studies have demonstrated no significant differences in survival rate, recurrence rate and type of recurrence between laparoscopic surgery for gastric cancer and conventional gastrectomy. The results of the aforementioned trials in early gastric cancer in Japan and Korea for which enrolment is complete remain to be published.

from Cancer via ola Kala on Inoreader http://ift.tt/22iyKf5
via IFTTT

Characteristics and overall survival of EGFR mutation-positive non-small cell lung cancer treated with EGFR tyrosine kinase inhibitors: a retrospective analysis for 1660 Japanese patients

Background

The Japan Guidelines of Lung Cancer Therapy recommend epidermal growth factor receptor-tyrosine kinase inhibitors as a first-line therapy for advanced/recurrent non-small cell lung cancer patients with epidermal growth factor receptor mutation. Although survival periods in recent reports of epidermal growth factor receptor-tyrosine kinase inhibitor treatment have been getting longer, the reasons why are unclear. We investigated the survival, prognostic factors and real-world treatment of non-small cell lung cancer patients with epidermal growth factor receptor mutation in clinical practice.

Methods

Non-small cell lung cancer patients (n = 1660) who started first-line treatment from January 2008 to December 2012 were enrolled. Patients were diagnosed with epidermal growth factor receptor mutation-positive advanced/recurrent non-small cell lung cancer by histology or cytology samples. The primary objective was to estimate overall survival. The secondary objectives were to determine prognostic factors, real-world treatment patterns and efficacy of gefitinib treatment. We calculated the treatment exposure rate for each treatment category using the following formula: exposure rate = person-years for the treatment category/total person-years x 100.

Results

The median overall survival was 30.8 months. Sex, age, histology, epidermal growth factor receptor mutation type, clinical stage and performance status affected overall survival. The exposure rates for all epidermal growth factor receptor-tyrosine kinase inhibitors, gefitinib and platinum-doublet chemotherapy were 62.1, 46.4 and 8.5% respectively. Overall 56.1% of patients were administered gefitinib as first-line therapy, and 39.0% were treated with ≥2 epidermal growth factor receptor-tyrosine kinase inhibitor regimens. The median progression-free survival in the first-line gefitinib group was 11.4 months. Factors affecting prognosis were sex, histology, clinical stage and performance status.

Conclusion

Epidermal growth factor receptor-tyrosine kinase inhibitors, especially gefitinib, are major components of the treatment regimens for epidermal growth factor receptor mutation-positive non-small cell lung cancer. Switching and re-challenging with epidermal growth factor receptor-tyrosine kinase inhibitors were also practiced in Japan.

from Cancer via ola Kala on Inoreader http://ift.tt/1NCOMxB
via IFTTT

The possibility of clinical sequencing in the management of cancer

Comprehensive genomic profiling using next-generation sequencing technologies provides insights into understanding the genomic architecture of human cancer. This new understanding of the cancer genome allows us to identify many more genomic alterations occurring within tumors than before, some of which could be potential therapeutic targets through molecular targeted agents. Currently, a large number of molecular targeted agents are being developed, and consequently, cancer treatment is rapidly shifting from empiric therapy employing cytotoxic anticancer drugs to genotype-directed therapy using molecular targeted agents. In current daily clinical practice, hotspot-based single-gene assays that detect RAS mutations in colorectal cancer or EGFR mutations in non-small cell lung cancer are widely used to identify variants. However, it is becoming evident that more comprehensive genomic analysis is crucial in identifying the patient population that may benefit from molecular targeted therapy and the accelerated development of novel drugs for early clinical trials. For these purposes, an increasing number of gene panel-based targeted sequencing is commercially available in clinical practice from sequencing companies. Despite several challenges in implementing this approach, comprehensive genomic profiling and identification of actionable mutations is likely to become one of the standard options in the management of cancer in the near future. The use of clinical sequencing has the potential to usher a new era in precision medicine for cancer diagnosis and treatment. In this review, we discuss the application of comprehensive genomic profiling using next-generation sequencing technologies in clinical oncology and address the current challenges for its implementation.

from Cancer via ola Kala on Inoreader http://ift.tt/22iyJYz
via IFTTT

A prospective study on the efficacy of two-dose influenza vaccinations in cancer patients receiving chemotherapy

Objective

Cancer patients receiving chemotherapy are at risk of acquiring influenza infections. Two-dose vaccination is a proposed strategy for increasing vaccination efficacy; however, this has yet to be confirmed in this population. The purpose of this study was to clarify the efficacy and safety of this strategy.

Methods

We conducted a multicentre prospective study on a two-dose vaccination regimen in cancer patients receiving chemotherapy. Second vaccinations were performed in patients who did not respond to all three viral strains after the first vaccination. Serum haemagglutination inhibition titres were measured to determine the patients' immunological response, 2 weeks prior to the first vaccination, 3–5 weeks after each vaccination, and at the end of the influenza season.

Results

We enrolled 109 patients, including 70 with solid tumours, 36 with haematological malignancies, and 3 with both cancer types. Among the total patients, the proportion of patients with protective titres against the three viral strains increased significantly from 3 to 27% (P < 0.01) following vaccination. Among the 79 patients who received a second vaccination, the proportion of those with protective titres against the individual strains increased by 10% (H1N1), 8% (H3N2), and 3% (B) compared with after the first vaccination. Serious adverse events were not observed.

Conclusions

We recommend influenza vaccinations for cancer patients, including those receiving chemotherapy. Also, the additional benefit of the second vaccination may be limited.

from Cancer via ola Kala on Inoreader http://ift.tt/1NCOOFJ
via IFTTT

A multicenter Phase II study evaluating the efficacy, safety and pharmacokinetics of trastuzumab emtansine in Japanese patients with heavily pretreated HER2-positive locally recurrent or metastatic breast cancer

Objective

Trastuzumab emtansine significantly improved progression-free survival and overall survival when compared with lapatinib–capecitabine in pretreated human epidermal growth factor receptor 2-positive advanced breast cancer. However, data in Japanese populations are limited.

Methods

In the single-arm Phase II JO22997 study, Japanese patients with human epidermal growth factor receptor 2-positive inoperable locally advanced/recurrent or metastatic breast cancer previously treated with at least one prior chemotherapy regimen for locally advanced/recurrent or metastatic breast cancer and trastuzumab in any setting received 3.6 mg/kg trastuzumab emtansine every 3 weeks until progression, unacceptable toxicity or consent withdrawal. The primary endpoint was Independent Review Committee-assessed objective response rate. Secondary endpoints included progression-free survival, overall survival, safety and pharmacokinetics.

Results

The objective response rate in 73 treated patients was 38.4% (90% confidence interval, 28.8–48.6%), exceeding the prespecified boundary for an objective response rate > 20%. After 6.5 months' median follow-up, median progression-free survival was 5.6 months (95% confidence interval, 4.6–8.2). After 28.9 months' median follow-up, median overall survival was 30.5 months (95% confidence interval 25.2–not reached). There were no treatment-related deaths. The most common Grade 3/4 adverse events were thrombocytopenia (22%) and aspartate aminotransferase elevations (14%). Thrombocytopenia did not require platelet transfusion and typically recovered before the next cycle. There were no substantial differences in trastuzumab emtansine or trastuzumab pharmacokinetic parameters between this study and previous data from non-Japanese patients.

Conclusions

JO22997 results suggest high activity of trastuzumab emtansine in Japanese patients, a safety profile consistent with previous studies in non-Japanese patients, no new safety signals and no evidence of pharmacokinetic differences between Japanese and non-Japanese populations. These results support trastuzumab emtansine therapy for Japanese patients with chemotherapy- and trastuzumab-pretreated human epidermal growth factor receptor 2-positive locally advanced/recurrent or metastatic breast cancer.

from Cancer via ola Kala on Inoreader http://ift.tt/22iyTPB
via IFTTT

DNA methyltransferase-3 like protein expression in various histological types of testicular germ cell tumor

Objective

DNA methyltransferase 3-like plays an important role in germ cell development. The aim of this study was to analyse the DNA methyltransferase 3-like protein expression in testicular germ cell tumors.

Methods

The immunohistochemical expression of DNA methyltransferase 3-like was examined in 86 testicular germ cell tumor specimens in various clinical settings. The association between DNA methyltransferase 3-like expression and disease stage was analyzed.

Results

DNA methyltransferase 3-like was strongly expressed in seven of the eight pure embryonal carcinomas (87.5%). Partial DNA methyltransferase 3-like expression was observed in 6 of 23 (26.1%) pure seminomas. Various degrees of DNA methyltransferase 3-like expression was observed in all four pure yolk sac tumors, of which three were prepubertal yolk sac tumors. In mixed germ cell tumors, DNA methyltransferase 3-like protein was expressed in various degrees in elements of the embryonal carcinoma (14/18, 77.8%), seminoma (4/11, 36.4%), teratoma (4/7, 57.1%) and choriocarcinoma (3/3, 100%) but not in the yolk sac tumors (0/4). When DNA methyltransferase 3-like expression was analyzed according to disease stages, it was significantly correlated with advanced seminoma rather than Stage I seminoma (46.2 vs. 0%, P = 0.019), whereas there was no significant difference in the DNA methyltransferase 3-like-positive proportion between Stage I and advanced disease in the mixed germ cell tumors.

Conclusions

Our findings suggest that DNA methyltransferase 3-like protein may play roles not only in the development of embryonal carcinoma but also in the development of advanced pure seminoma and pure yolk sac tumor.

from Cancer via ola Kala on Inoreader http://ift.tt/1NCP1Zs
via IFTTT

Effect of olanzapine for breast cancer patients resistant to triplet antiemetic therapy with nausea due to anthracycline-containing adjuvant chemotherapy

Objective

Triplet antiemetic therapy with neurokinin 1 receptor blocker, 5-hydroxytryptamine receptor blocker and steroids is commonly used in patients who are highly emetic after chemotherapy. However, an alternative antiemetic therapy for patients who are resistant to triplet antiemetic therapy is not established. Olanzapine is recommended in the guidelines as an optional antiemetic drug. However, the effectiveness of adding olanzapine to triplet antiemetic therapy is unknown. In this study, the effectiveness and safety of adding olanzapine to triplet antiemetic therapy with aprepitant, palonosetron and dexamethasone as highly emetic anthracycline-containing adjuvant chemotherapy for primary breast cancer patients were prospectively investigated.

Methods

Forty-five patients with breast cancer who experienced >Grade 1 nausea or any vomiting after the first cycle of chemotherapy using both epirubicin and cyclophosphamide were included. Low-dose olanzapine (2.5 mg/day) was administered orally from the first day of chemotherapy for 4 days, and the number of episodes of vomiting, scale of nausea, dietary intake and somnolence were compared with the symptoms after the first cycle.

Results

As the primary endpoint, the nausea grade was significantly improved by adding olanzapine (P < 0.05). As the secondary endpoints, mean nausea scale (3.2->1.9, Day 1; 3->1.3–1, Days 2–6) and dietary intake (33.6->53.8%, Day 1; 42.0->60.7–78.1%, Days 2–6) were improved by adding olanzapine. Only four patients withdrew due to somnolence and/or dizziness.

Conclusions

This study demonstrated the effectiveness and tolerability of adding low-dose olanzapine for patients with insufficient nausea relief with triplet antiemetic therapy consisting of palonosetron, steroid and aprepitant.

from Cancer via ola Kala on Inoreader http://ift.tt/22iyuwy
via IFTTT

IN THIS ISSUE

from Cancer via ola Kala on Inoreader http://ift.tt/1NCP47A
via IFTTT

Plasma ghrelin levels as a predictor of adverse renal events due to cisplatin-based chemotherapy in patients with esophageal cancer

Objective

Although combination chemotherapy with docetaxel, cisplatin and 5-fluorouracil demonstrates high response rates in esophageal squamous cell carcinoma, patients treated with docetaxel, cisplatin and 5-fluorouracil frequently experience acute kidney injury. Ghrelin has shown renal protective effects in an experimental acute kidney injury model by reducing tubular apoptosis. In this prospective observational study, we evaluated the association between plasma ghrelin concentrations and docetaxel, cisplatin and 5-fluorouracil-related acute kidney injury.

Methods

Forty consecutive patients with esophageal squamous cell carcinoma who received docetaxel, cisplatin and 5-fluorouracil from October 2013 to July 2014 were enrolled in this study. Serum creatinine and urinary α-1 microglobulin, a marker of renal tubular damage, were measured six times during chemotherapy.

Results

The increases of creatinine level which is defined in Common Terminology Criteria for Adverse Event were observed less frequently in patients with acyl ghrelin concentrations of ≥9.6 fmol/ml (HAG group) than in those with concentrations <9.6 fmol/ml on Day 2 (LAG group) (P= 0.024). Serum creatinine was significantly lower in the HAG group than in the LAG group (Day 8: 0.79 ± 0.16 vs. 0.97 ± 0.26, P = 0.024; Day 11: 0.85 ± 0.19 vs. 1.08 ± 0.34 mg/dl, P = 0.049). Urinary α-1 microglobulin levels were significantly lower in the HAG group than in the LAG group (Day 4: 2.48 ± 1.83 vs. 3.33 ± 1.41, P = 0.011; Day 8: 4.67 ± 5.50 vs. 5.09 ± 2.54, P = 0.011; Day 11: 11.55 ± 13.78 vs. 16.43 ± 17.84 mg/l, P = 0.020).

Conclusions

Plasma acyl ghrelin concentrations on Day 2 of chemotherapy may be a potential predictor of docetaxel, cisplatin and 5-fluorouracil-induced acute kidney injury.

from Cancer via ola Kala on Inoreader http://ift.tt/22iyBrU
via IFTTT

Assessment of quality of life of children and adolescents with cancer during their treatment

Objective

The purpose of this study was to evaluate the quality of life of children and adolescents with any type of cancer in all phases of their treatment.

Methods

Fifty-six newly diagnosed patients diagnosed with malignancy and hospitalized in a Pediatric Hematology-Oncology Unit in Athens were included in the study. Minneapolis-Manchester Quality of Life Instrument was used for data collection from July 2010 to December 2012. The assessment of children and adolescents' quality of life who were under treatment was performed in three different stages of treatment.

Results

The results of the study showed that the quality of life of children and adolescents with cancer did not change notably during their treatment (F = 0.16, P = 0.86 and F = 0.03, P = 0.97). For the first measurement, at the beginning of the therapy, the score on the scale for quality of life for children and adolescents was 3.44 and 3.88, respectively, in the middle of the treatment 3.36 and 3.89, respectively, and 3.43 and 3.89, respectively, when therapy was completed. Children and adolescents diagnosed with hematologic cancer stated higher quality of life scores (z = –1.61, P = 0.05 and t = 2.64, P = 0.007). Moreover, teenage patients (F = 13.22, P = 0.001) and male patients (t = 2.31, P = 0.02 and t = 2.27, P = 0.02) expressed better quality-of-life scores.

Conclusion

According to the results, children and adolescents with any kind of cancer have better quality-of-life scores at the end of their treatment, and when they are supported by their family.

from Cancer via ola Kala on Inoreader http://ift.tt/1NCP086
via IFTTT

5-Hydroxymethylcytosine expression is associated with poor survival in cervical squamous cell carcinoma

Objective

Deoxyribonucleic acid methylation is an important epigenetic modification that is frequently altered in cancer. Recent reports showed that the level of 5-hydroxymethylcytosine was altered in various types of cancers. The influence of deoxyribonucleic acid methylation in cervical squamous cell carcinoma is not fully understood. In this study, we investigated 5-hydroxymethylcytosine and ten–eleven translocation expression in cervical squamous cell carcinoma and whether they are associated with poor survival in cervical squamous cell carcinoma.

Methods

We detected the expression of 5-hydroxymethylcytosine, 5-methylcytosine and TET1/2/3 in 140 patients with cervical squamous cell carcinoma and 40 patients with normal cervical tissues by immunohistochemistry. We assessed the prognostic values of 5-hydroxymethylcytosine, 5-methylcytosine and TET2 in the clinical outcome of cervical squamous cell carcinoma.

Results

Expression of 5-hydroxymethylcytosine was significantly decreased in cervical squamous cell carcinoma compared with normal cervix tissues. In contrast, 5-methylcytosine expression was significantly increased in cervical squamous cell carcinoma compared with normal cervix tissues. Moreover, expression of TET2, but not TET1 and TET3, was decreased in cervical squamous cell carcinoma. Our study showed that the decreased level of 5-hydroxymethylcytosine predicts poor prognosis of cervical squamous cell carcinoma patients. The expression of 5-hydroxymethylcytosine was an independent prognostic factor for both disease-free and overall survival of cervical squamous cell carcinoma patients.

Conclusions

In cervical squamous cell carcinoma, less aggressive tumor behavior was correlated with 5-hydroxymethylcytosine and TET2. Our data indicated that 5-hydroxymethylcytosine may become a prognostic marker for cervical squamous cell carcinoma and the decreased expression of TET2 may be an underlying mechanism for decreased 5-hmC in cervical squamous cell carcinoma.

from Cancer via ola Kala on Inoreader http://ift.tt/22iyFI8
via IFTTT

Diversity in treatment modalities of Stage II/III urothelial cancer in Japan: sub-analysis of the multi-institutional national database of the Japanese Urological Association

Objective

We aimed to survey treatment modalities for the patients with Stage II/III urothelial cancer in Japan.

Methods

We used the multi-institutional national database of the Japanese Urological Association from 348 Japanese institutions, in which a total of 3707 patients with muscle-invasive bladder cancer and 1538 with upper urinary tract urothelial carcinoma were registered in 2008 and 2011, respectively. Primary treatment was classified as surgery alone, surgery with chemotherapy, surgery with radiation, radiation alone, chemotherapy alone, combination of radiation and chemotherapy and observation. Overall and cancer-specific survivals were examined using the Kaplan–Meier method, and survival in the subgroups was analyzed using the log-rank test.

Results

In Stage II/III bladder cancer patients, 49.7% of those were treated with radical operation and 22.3% received observation only. A total 97.2% of Stage II/III upper urinary tract urothelial carcinoma patients treated with radical surgery. A total 30.4% of Stage II/III bladder cancer patients received chemotherapy. Majority of the patients received cisplatin-based regimen, however, regimens of chemotherapy was rich in variety up to 13 regimens. Chemotherapy regimens for the patients with upper urinary tract urothelial carcinoma were also various up to eight regimens. Overall and cancer-specific survivals were statistically significantly stratified according to the clinical stage. The upper urinary tract urothelial carcinoma patients diagnosed with clinical stage T3 had significantly poor prognosis compared with those diagnosed with clinical stage T2.

Conclusions

This study demonstrated the variety of treatments used for Japanese patients with Stage II/III urothelial cancer. Treatment standardization for these entities may be necessary.

from Cancer via ola Kala on Inoreader http://ift.tt/1NCPcEg
via IFTTT

Repeat biopsy of primary disease negatively affects the outcome of patients with nasopharyngeal cancer treated with definitive intensity-modified radiotherapy: a cohort analysis of 795 patients

Objective

To determine whether pretreatment repeat biopsy of nasopharynx is associated with an impaired outcome in nasopharyngeal carcinoma patients in an intensity-modified radiotherapy era.

Methods

We performed a retrospective data review of the association between pretreatment nasopharyngeal biopsy and outcomes for all nasopharyngeal carcinoma patients treated at our center between January 2007 and December 2011. Of the 720 patients enrolled, 693 (96.3%) were diagnosed after initial biopsy and 27 (3.7%) after repeat biopsy. Five-year cancer-specific survival, disease-free survival and distant metastasis-free survival for the two groups were compared using univariate and multivariate analyses to evaluate the effects of repeat biopsy on the outcome.

Results

Five-year estimated cancer-specific survival (75.9 vs. 88.5%, P= 0.045) and disease-free survival (63.3 vs. 77.1%, P= 0.041) were significantly poorer in the repeat biopsy group than the initial biopsy group. After adjustment for other prognostic factors (age, gender, T and N stage), pretreatment biopsy remained independently associated with poorer both 5-year cancer-specific survival and disease-free survival. The hazard ratios for cancer-specific survival and disease-free survival in the repeat biopsy group were 2.73 (95% confidence interval 1.09–6.82) and 2.22 (95% confidence interval 1.12–4.37) compared with the initial biopsy group (reference), respectively. The repeat biopsy group also had a higher risk of distant failure compared with the initial biopsy group (hazard ratio 2.82, 95% confidence interval 1.22–6.51, P= 0.015).

Conclusion

Pretreatment repeat biopsy of nasopharynx has a detrimental effect on survivals of nasopharyngeal carcinoma patients, which may be partly due to an increased frequency of distant metastasis.

from Cancer via ola Kala on Inoreader http://ift.tt/22iyH2L
via IFTTT

The Japanese Guidelines for Breast Cancer Screening

Objective

The incidence of breast cancer has progressively increased, making it the leading cause of cancer deaths in Japan. Breast cancer accounts for 20.4% of all new cancers with a reported age-standardized rate of 63.6 per 100 000 women.

Methods

The Japanese guidelines for breast cancer screening were developed based on a previously established method. The efficacies of mammography with and without clinical breast examination, clinical breast examination and ultrasonography with and without mammography were evaluated. Based on the balance of the benefits and harms, recommendations for population-based and opportunistic screenings were formulated.

Results

Five randomized controlled trials of mammographic screening without clinical breast examination were identified for mortality reduction from breast cancer. The overall relative risk for women aged 40–74 years was 0.75 (95% CI: 0.67–0.83). Three randomized controlled trials of mammographic screening with clinical breast examination served as eligible evidence for mortality reduction from breast cancer. The overall relative risk for women aged 40–64 years was 0.87 (95% confidence interval: 0.77–0.98). The major harms of mammographic screening were radiation exposure, false-positive cases and overdiagnosis. Although two case–control studies evaluating mortality reduction from breast cancer were found for clinical breast examination, there was no study assessing the effectiveness of ultrasonography for breast cancer screening.

Conclusions

Mammographic screening without clinical breast examination for women aged 40–74 years and with clinical breast examination for women aged 40–64 years is recommended for population-based and opportunistic screenings. Clinical breast examination and ultrasonography are not recommended for population-based screening because of insufficient evidence regarding their effectiveness.

from Cancer via ola Kala on Inoreader http://ift.tt/1NCP7jU
via IFTTT

Attitudes towards second opinion services in cancer care: a nationwide survey of oncologists in Korea

Objective

Second opinion is a common phenomenon in many health systems, especially in the care of patients with cancer. However, it is not clear whether second opinion seeking should be promoted or discouraged and how second opinion services and policies can be better formalized to maximize the benefits and minimize the disadvantages.

Methods

A nationwide survey was conducted with a representative sample of 678 physicians involved in cancer care (75.5% participation rate) recruited in 13 cancer centres.

Results

Most physicians involved with cancer care perceived patients' second opinion seeking as a legitimate right (96.0%) and they acknowledged the need for second opinion services under certain conditions (98.2%). Many believed that second opinions can enhance patient satisfaction (77.3%) and quality of care (74.3%), but they also had concerns about increase in healthcare and societal costs (91.3%) and concentration in a high-volume centre (90.7%). While the majority agreed with the involvement of the first opinion physicians in the second opinion services (69.5%), there were mixed opinions regarding the desirability of remote (teleconsultation) second opinion services (49.0%) and coverage by national health insurance (51.9%).

Conclusion

Physicians were generally positive to second opinion services and expected positive consequences in terms of patient satisfaction and quality of care. However, they had concerns about the consequences regarding cost and equity, and disagreements were observed regarding the way to improve second opinion services. The physicians' opinions revealed in our study will be helpful in developing clearer guidelines used to maximize the benefits of second opinion services.

from Cancer via ola Kala on Inoreader http://ift.tt/22iyEE5
via IFTTT

Cancer incidence rate in Japanese in Japan and in the United States from the Cancer Incidence in Five Continents

from Cancer via ola Kala on Inoreader http://ift.tt/1NCOTcx
via IFTTT

Initial emergencies in children and adolescents with malignant hematologic–oncological diseases

Summary

During the last few decades cure rates in children and adolescents with malignant diseases have approached 75–80 %. While this has been mainly achieved by a reduction of relapses, nowadays, prevention of disease- and therapy-related deaths has come more and more into focus. Initial emergencies in pediatric hematology and oncology represent rare but life-threatening situations which can be recognized by the combination of a patient's medical history, age, clinical symptoms, laboratory parameters, and imaging studies. In the present review, both disease- and therapy-related oncological emergencies will be described including tracheal collapse and superior vena cava syndrome in case of mediastinal tumors, intussusception and inferior vena cava syndrome in case of abdominal tumors, intracranial hypertension in brain tumors, spinal cord compression in case of dumbbell tumors as well as tumor lysis syndrome and coagulation disorders. Possible differential diagnoses of malignant diseases and type and risk of the diagnostic procedures will be described in detail, emphasizing that all diagnostic procedures should be done appropriately and rapidly at experienced and specialized pediatric hematologic–oncological institutions in order to prevent fatality or irreversible damage.

from Cancer via ola Kala on Inoreader http://ift.tt/1U4BIjC
via IFTTT

SEOM/SERAM consensus statement on radiological diagnosis, response assessment and follow-up in colorectal cancer

Abstract

Colorectal cancer (CRC) is one of the world's most common cancers, and has one of the highest mortality rates. The last few decades have seen great progress in preventing, diagnosing and treating this disease, providing undeniable impact on patients' prognosis and quality of life. At all these stages of CRC management, imaging techniques play an essential role. This article reviews some important issues concerning the use of various radiological techniques in the screening, diagnosis, staging, assessment of treatment response, and follow-up of patients with CRC. It also includes a number of practical recommendations on indications for use, technical requirements, minimum information required in the radiology report, evaluation criteria for the response to various drugs, and the recommended frequency at which different examinations should be performed. This consensus statement is the result of cooperation between the Spanish Society of Medical Oncology (SEOM) and the Spanish Society of Radiology (SERAM).

from Cancer via ola Kala on Inoreader http://ift.tt/1qyJBnc
via IFTTT

Usefulness of the preoperative platelet count in the diagnosis of adnexal tumors

Abstract

Platelets seem to play a role in the development of ovarian cancer. Platelet count (PLT) is an ubiquitous available parameter. We analyzed retrospectively data of 756 patients with primary adnexal tumors: 584 benign and 172 malignant (148 invasive and 24 borderline) cases. We compared the diagnostic accuracy of CA125, PLT, and a combination of CA125 and PLT. The cutoff values for CA125 and PLT were 35 U/ml and 350/nl, respectively. The median age of patients with benign and malignant tumors was 45 and 64 years, respectively. A total of 77/172 (44.8 %) malignant and 50/584 (8.6 %) benign cases presented with thrombocytosis (PLT ≥350/nl). The median PLT differed between benign and malignant cases (257/nl vs. 330/nl; p < 0.001), similarly as CA125 did (17 vs. 371 U/ml; p < 0.001). In the multivariate analysis, age, CA125, and thrombocytosis predicted independently the presence of malignancy. The results of CA125 were false positive in 21 % and false negative in 13 %. If considered together, thrombocytosis + CA125 were false positive only in 9 %, whereas the false negative rate was 12 %. The sensitivity and specificity of CA125, thrombocytosis, and thrombocytosis + CA125 for detecting adnexal malignancy were 0.88/0.78, 0.45/0.91, and 0.81/0.94, respectively. The positive predictive value (PPV) of CA125, thrombocytosis, and thrombocytosis + CA125 was 0.79, 0.61, and 0.91, respectively. In conclusion, PLT is an ubiquitously available parameter that could be useful in the diagnostic evaluation of pelvic mass. Considering thrombocytosis additionally to CA125 improves the specificity and PPV and reduces the false positive rate in detecting adnexal malignancy.

from Cancer via ola Kala on Inoreader http://ift.tt/1YJqhiQ
via IFTTT

The clinical significance of changes in ezrin expression in osteosarcoma of children and young adults

Abstract

Ezrin is a protein that functions as a cross-linker between actin cytoskeleton and plasma membrane. Its clinical role in osteosarcoma is unclear. The aim of this study was to investigate, in osteosarcoma, the prognostic value of ezrin expression at biopsy and changes in expression levels after preoperative chemotherapy. Thirty-eight newly diagnosed osteosarcoma patients aged 6–23 years were included. At diagnosis, 20 patients had localized disease, the others had distant metastases. Median follow-up was 75 months (range 13–135). Ezrin expression was assessed immunohistochemically in biopsy tissue and primary tumour specimens resected after chemotherapy. The influence on survival of changes in ezrin expression after chemotherapy was analysed. Ezrin expression was significantly higher after preoperative chemotherapy and changes compared to biopsy tissue were significantly lower in patients with early progression than in patients with relapse or no further evidence of disease (p = 0.006 and p = 0.002, respectively). Similarly, ezrin expression was higher after preoperative chemotherapy and exhibited less change in expression in deceased patients compared to patients surviving more than 5 years (both p = 0.001). Ezrin expression at biopsy was significantly associated with both histopathological aggressiveness (p < 0.001) and tumour size (p = 0.037). The results of this study provide evidence that changes in overexpression of ezrin due to preoperative chemotherapy could be a useful predictive and prognostic marker in patients with osteosarcoma.

from Cancer via ola Kala on Inoreader http://ift.tt/1W6SQcf
via IFTTT

Phase I study to evaluate toxicity and feasibility of intratumoral injection of α-gal glycolipids in patients with advanced melanoma

Abstract

Effective uptake of tumor cell-derived antigens by antigen-presenting cells is achieved pre-clinically by in situ labeling of tumor with α-gal glycolipids that bind the naturally occurring anti-Gal antibody. We evaluated toxicity and feasibility of intratumoral injections of α-gal glycolipids as an autologous tumor antigen-targeted immunotherapy in melanoma patients (pts). Pts with unresectable metastatic melanoma, at least one cutaneous, subcutaneous, or palpable lymph node metastasis, and serum anti-Gal titer ≥1:50 were eligible for two intratumoral α-gal glycolipid injections given 4 weeks apart (cohort I: 0.1 mg/injection; cohort II: 1.0 mg/injection; cohort III: 10 mg/injection). Monitoring included blood for clinical, autoimmune, and immunological analyses and core tumor biopsies. Treatment outcome was determined 8 weeks after the first α-gal glycolipid injection. Nine pts received two intratumoral injections of α-gal glycolipids (3 pts/cohort). Injection-site toxicity was mild, and no systemic toxicity or autoimmunity could be attributed to the therapy. Two pts had stable disease by RECIST lasting 8 and 7 months. Tumor nodule biopsies revealed minimal to no change in inflammatory infiltrate between pre- and post-treatment biopsies except for 1 pt (cohort III) with a post-treatment inflammatory infiltrate. Two and four weeks post-injection, treated nodules in 5 of 9 pts exhibited tumor cell necrosis without neutrophilic or lymphocytic inflammatory response. Non-treated tumor nodules in 2 of 4 evaluable pts also showed necrosis. Repeated intratumoral injections of α-gal glycolipids are well tolerated, and tumor necrosis was seen in some tumor nodule biopsies after tumor injection with α-gal glycolipids.

from Cancer via ola Kala on Inoreader http://ift.tt/1YJq8vW
via IFTTT

CTLA-4 in mesothelioma patients: tissue expression, body fluid levels and possible relevance as a prognostic factor

Abstract

CTLA-4 function as a negative regulator of T cell-mediated immune response is well established, whereas much less is known about the immunoregulatory role of its soluble isoform (sCTLA-4). No data are available on CTLA-4 expression and prognostic impact in malignant pleural mesothelioma (MPM). We investigated, by immunohistochemistry, CTLA-4 expression in tumor tissues and, by ELISA, sCTLA-4 levels in sera and matched pleural effusions from 45 MPM patients. Prognostic effect of CTLA-4 expression on overall survival (OS) was assessed through Cox regression and prognostic significance expressed as death rate ratio (HR). We found that 56.0 % of MPM tissues expressed CTLA-4 with variable intensity and percentage of positive cells estimated by the immunoreactive score. sCTLA-4 levels were significantly higher in sera (S-sCTLA-4) than in pleural effusions (PE-sCTLA-4) (geometric mean ratio = 2.70, P value = 0.020). CTLA-4 expression at the tissue level was higher in the epithelioid histological subtype than in the sarcomatoid, whereas at the serum level, it was higher in the sarcomatoid subtype. A homogeneous favorable prognostic effect was found for CTLA-4 overexpression in tissue, serum and pleural effusion. Interestingly, only the PE-sCTLA-4 was found to be a statistically significant positive prognostic factor (HR = 0.37, 95 % CI = 0.18–0.77, P value = 0.007). Indeed, PE-sCTLA-4 correlated with CTLA-4 expression in tissues, whereas this latter expression showed a weak association with OS. To confirm our findings, further experimental evidences obtained from a larger cohort of MPM patients are required. However, our results would indicate a positive correlation of PE-sCTLA-4 levels and OS in MPM patients.

from Cancer via ola Kala on Inoreader http://ift.tt/1W6SOAY
via IFTTT

Understanding the biosimilar approval and extrapolation process—A case study of an epoetin biosimilar

Publication date: Available online 20 May 2016
Source:Critical Reviews in Oncology/Hematology
Author(s): Amit B. Agarwal, Ali McBride
The World Health Organization defines a biosimilar as "a biotherapeutic product which is similar in terms of quality, safety and efficacy to an already licensed reference biotherapeutic product." Biosimilars are biologic medical products that are very distinct from small-molecule generics, as their active substance is a biological agent derived from a living organism. Approval processes are highly regulated, with guidance issued by the European Medicines Agency and US Food and Drug Administration. Approval requires a comparability exercise consisting of extensive analytical and preclinical in vitro and in vivo studies, and confirmatory clinical studies. Extrapolation of biosimilars from their original indication to another is a feasible but highly stringent process reliant on rigorous scientific justification. This review focuses on the processes involved in gaining biosimilar approval and extrapolation and details the comparability exercise undertaken in the European Union between originator erythropoietin-stimulating agent, Eprex^®, and biosimilar, Retacrit™.



from Cancer via ola Kala on Inoreader http://ift.tt/1U5xyoX
via IFTTT

Targeting Notch degradation system provides promise for breast cancer therapeutics

Publication date: Available online 20 May 2016
Source:Critical Reviews in Oncology/Hematology
Author(s): Jing Liu, Jia-Xin Shen, Xiao-Fen Wen, Yu-Xian Guo, Guo-Jun Zhang
Notch receptor signaling pathways play an important role, not only in normal breast development but also in breast cancer development and progression. As a group of ligand-induced proteins, different subtypes of mammalian Notch (Notch1-4) are sensitive to subtle changes in protein levels. Thus, a clear understanding of mechanisms of Notch protein turnover is essential for understanding normal and pathological mechanisms of Notch functions. It has been suggested that there is a close relationship between the carcinogenesis and the dysregulation of Notch degradation. However, this relationship remains mostly undefined in the context of breast cancer, as protein degradation is mediated by numerous signaling pathways as well as certain molecule modulators (activators/inhibitors). In this review, we summarize the published data regarding the regulation of Notch family member degradation in breast cancer, while emphasizing areas that are likely to provide new therapeutic modalities for mechanism-based anti-cancer drugs.



from Cancer via ola Kala on Inoreader http://ift.tt/1WGPLj1
via IFTTT

A phase I study of mTOR inhibitor everolimus in association with cisplatin and radiotherapy for the treatment of locally advanced cervix cancer: PHOENIX I

Abstract

Background

Cervix cancer (CC) represents the fourth most common cancer in women. Treatment involving cisplatin and radiotherapy has been the standard for locally advanced disease. Everolimus inhibits the aberrant activity of mTOR that is part of carcinogenesis in CC. Further everolimus inactivates the HPV E7 oncoprotein and inhibits its proliferation. Preclinical models have suggested that everolimus sensitizes tumoral cells and vasculature to cisplatin and radiotherapy.

Methods

In a 3 + 3 design, the trial aimed to treat three dose levels of at least three patients with daily doses of everolimus (2.5, 5 and 10 mg/day), cisplatin and radiotherapy delivered in a 9-week interval in CC patients, stage IIB, IIIA or IIIB. Patients received everolimus from day −7 up to the last day of brachytherapy. Primary objective was to evaluate safety, toxicity and the maximum-tolerated dose (MTD) of everolimus in association with cisplatin and radiotherapy. Pharmacokinetic (PK) parameters and response rates were analyzed as secondary objectives.

Results

Thirteen patients were enrolled, 6 at 2.5 mg, 3 at 5 mg and 4 at 10 mg. Four patients did not complete the planned schedule, 1 at 2.5 mg presented grade 4 acute renal failure interpreted as dose-limiting toxicity (DLT) and 3 at 10 mg: 1 with disease progression, and 2 with DLTs—1 grade 3 rash and 1 grade 4 neutropenia. PK results were characterized by dose-dependent increases in AUC and C _max.

Conclusions

The MTD of everolimus in combination with cisplatin and radiotherapy has been defined as 5 mg/day. The data regarding safety and response rates support further studies.

from Cancer via ola Kala on Inoreader http://ift.tt/256sKrp
via IFTTT

Usefulness of the preoperative platelet count in the diagnosis of adnexal tumors

Abstract

Platelets seem to play a role in the development of ovarian cancer. Platelet count (PLT) is an ubiquitous available parameter. We analyzed retrospectively data of 756 patients with primary adnexal tumors: 584 benign and 172 malignant (148 invasive and 24 borderline) cases. We compared the diagnostic accuracy of CA125, PLT, and a combination of CA125 and PLT. The cutoff values for CA125 and PLT were 35 U/ml and 350/nl, respectively. The median age of patients with benign and malignant tumors was 45 and 64 years, respectively. A total of 77/172 (44.8 %) malignant and 50/584 (8.6 %) benign cases presented with thrombocytosis (PLT ≥350/nl). The median PLT differed between benign and malignant cases (257/nl vs. 330/nl; p < 0.001), similarly as CA125 did (17 vs. 371 U/ml; p < 0.001). In the multivariate analysis, age, CA125, and thrombocytosis predicted independently the presence of malignancy. The results of CA125 were false positive in 21 % and false negative in 13 %. If considered together, thrombocytosis + CA125 were false positive only in 9 %, whereas the false negative rate was 12 %. The sensitivity and specificity of CA125, thrombocytosis, and thrombocytosis + CA125 for detecting adnexal malignancy were 0.88/0.78, 0.45/0.91, and 0.81/0.94, respectively. The positive predictive value (PPV) of CA125, thrombocytosis, and thrombocytosis + CA125 was 0.79, 0.61, and 0.91, respectively. In conclusion, PLT is an ubiquitously available parameter that could be useful in the diagnostic evaluation of pelvic mass. Considering thrombocytosis additionally to CA125 improves the specificity and PPV and reduces the false positive rate in detecting adnexal malignancy.

from Cancer via ola Kala on Inoreader http://ift.tt/1YJqhiQ
via IFTTT

The clinical significance of changes in ezrin expression in osteosarcoma of children and young adults

Abstract

Ezrin is a protein that functions as a cross-linker between actin cytoskeleton and plasma membrane. Its clinical role in osteosarcoma is unclear. The aim of this study was to investigate, in osteosarcoma, the prognostic value of ezrin expression at biopsy and changes in expression levels after preoperative chemotherapy. Thirty-eight newly diagnosed osteosarcoma patients aged 6–23 years were included. At diagnosis, 20 patients had localized disease, the others had distant metastases. Median follow-up was 75 months (range 13–135). Ezrin expression was assessed immunohistochemically in biopsy tissue and primary tumour specimens resected after chemotherapy. The influence on survival of changes in ezrin expression after chemotherapy was analysed. Ezrin expression was significantly higher after preoperative chemotherapy and changes compared to biopsy tissue were significantly lower in patients with early progression than in patients with relapse or no further evidence of disease (p = 0.006 and p = 0.002, respectively). Similarly, ezrin expression was higher after preoperative chemotherapy and exhibited less change in expression in deceased patients compared to patients surviving more than 5 years (both p = 0.001). Ezrin expression at biopsy was significantly associated with both histopathological aggressiveness (p < 0.001) and tumour size (p = 0.037). The results of this study provide evidence that changes in overexpression of ezrin due to preoperative chemotherapy could be a useful predictive and prognostic marker in patients with osteosarcoma.

from Cancer via ola Kala on Inoreader http://ift.tt/1W6SQcf
via IFTTT

NATCON IASO Abstract 2015

from Cancer via ola Kala on Inoreader http://ift.tt/1Xo0Zbh
via IFTTT

Rationale of Technical Requirements for NRG-BR001: The First NCI-Sponsored Trial of SBRT for the Treatment of Multiple Metastases

Publication date: Available online 20 May 2016
Source:Practical Radiation Oncology
Author(s): Hania A. Al-Hallaq, Steven Chmura, Joseph K. Salama, Kathryn A. Winter, Clifford G. Robinson, Thomas M. Pisansky, Virginia Borges, Jessica L. Lowenstein, Susan McNulty, James M. Galvin, David S. Followill, Robert D. Timmerman, Julia R. White, Ying Xiao, Martha M. Matuszak
IntroductionIn 2014, the NRG Oncology Group initiated the first NCI-sponsored, phase I clinical trial of SBRT for the treatment of multiple metastases in multiple organ sites (XXXX; NCTXXX). The primary endpoint is to test the safety of SBRT for the treatment of multiple lesions (2-4) in several anatomic sites in a multi-institutional setting. Because of the technical challenges inherent to treating multiple lesions as their spatial separation decreases, we present the technical requirements for NRG-XXXX and the rationale for their selection.Methods and MaterialsPatients with controlled primary tumors of breast, non-small cell lung, or prostate are eligible if they have 2-4 metastases distributed among 7 extracranial anatomic locations throughout the body. Prescription and organ-at-risk (OAR) doses were determined by expert consensus. Credentialing requirements include 1) irradiation of the IROC phantom with SBRT, 2) submitting IGRT case studies, and 3) planning the benchmark. Guidelines for navigating challenging planning cases including assessing composite dose are discussed.ResultsDosimetric planning to multiple lesions receiving differing doses (45-50Gy) and fractionation (3-5) while irradiating the same organs-at-risk is discussed, particularly for metastases in close proximity (≤5cm). The benchmark case was selected to demonstrate the planning trade-offs required to satisfy protocol requirements for two nearby lesions. Examples of passing benchmark plans exhibited a large variability in plan conformity.DiscussionNRG-XXXX was developed using expert consensus on multiple issues from the dose fractionation regimen to the minimum IGRT guidelines. Credentialing was tied to the task rather than the anatomic site in order to reduce its burden. Every effort was made to include a variety of delivery methods to reflect current SBRT technology. While some simplifications were adopted, the successful completion of this trial will inform future designs of both national and institutional would allow immediate clinical adoption of SBRT trials for oligometastases.



from Cancer via ola Kala on Inoreader http://ift.tt/1W6Ny0b
via IFTTT

Combined assessment of EGFR-related molecules to predict outcome of 1st-line cetuximab-containing chemotherapy for metastatic colorectal cancer

10.1080/15384047.2016.1178426<br/>Yu Sunakawa

from Cancer via ola Kala on Inoreader http://ift.tt/27GSPiZ
via IFTTT

Suppression of pancreatic ductal adenocarcinoma growth by intratumoral delivery of attenuated Salmonella typhimurium using a dual fluorescent live tracking system

10.1080/15384047.2016.1177683<br/>Sujin Zhou

from Cancer via ola Kala on Inoreader http://ift.tt/1ODdadw
via IFTTT

HIF-1α inhibition by 2-methoxyestradiol induces cell death via activation of the mitochondrial apoptotic pathway in acute myeloid leukemia

10.1080/15384047.2016.1177679<br/>Nana Zhe

from Cancer via ola Kala on Inoreader http://ift.tt/27GSCwo
via IFTTT

Promoting quality care in cancer patients with Limited English Proficiency: Perspectives of medical interpreters

from Cancer via ola Kala on Inoreader http://ift.tt/1TtXM8Q
via IFTTT

Central nervous system relapse in patients with untreated her2-positive esophageal or gastroesophageal junction adenocarcinoma

Abstract

Although HER2-positive breast cancers demonstrate a propensity for central nervous system (CNS) metastasis, it is unknown whether other HER2-positive tumors, including adenocarcinomas of the esophagus/gastroesophageal junction (EAC), share this characteristic. Insight into this association may inform the development of HER2-targeted therapies that penetrate the blood-brain barrier. We examined HER2 overexpression and gene amplification in 708 patients with EAC who underwent curative-intent surgery during a time period (1980-1997) when no patient received HER2-targeted therapy. We identified patients whose site of first cancer recurrence was CNS and those who had a CNS relapse at any time. After a median follow-up of 61.2 months, 3.4% (24/708) of patients developed CNS relapse (all involved the brain). Patients with HER2-positive (vs -negative) primary tumors showed a higher 5-year cumulative incidence of CNS relapse as first recurrence (5.8% vs 1.2%; P =.0058) and at any time (8.3% vs 2.4%; P =.0062). In a multivariable model that included covariates previously associated with HER2 or with CNS relapse in breast cancer, HER2 positivity was the only variable that was statistically significantly associated with shorter time to CNS relapse as first recurrence (P =.0026) or at any time (hazard ratio 4.3 [95% confidence interval 1.8 to 10.3]; P =.001). These are the first data in a non-breast cancer to demonstrate an association between HER2 positivity and higher CNS relapse risk after surgery, and suggest that HER2-positive EACs have a predilection for CNS metastases. This article is protected by copyright. All rights reserved.

from Cancer via ola Kala on Inoreader http://ift.tt/1qyaNSZ
via IFTTT

Routine sampling of internal mammary lymph nodes during microsurgical breast reconstruction—Experience based on 524 microsurgical breast reconstructions

Purpose

Exploration of the internal mammary vessels during microsurgical reconstruction presents an ideal opportunity for identifying and sampling the internal mammary lymph node (IMLN) basin.

Methods

A retrospective review of patients undergoing microsurgical breast reconstruction using the internal mammary vessels as recipient vessels was conducted from March 2000 to December 2014. Patient demographics, tumor characteristics, preoperative lymph node mapping, reconstructive timing, and outcomes were studied.

Results

A total of 524 microsurgical breast reconstructions in 516 patients were performed using the internal mammary vessels. IMLNs were sampled in 53 immediate and 42 delayed breast reconstructions. Eight (seven in the immediate and one in the delayed group) of the sampled nodes were positive for cancer metastasis, for an incidence of 8.4% in identified lymph nodes. All patients with metastatic IMLNs subsequently received local-regional radiation and chemotherapy. All patients were alive, and six were disease-free at the conclusion of the study period, which had an average follow up of 67.3 months.

Conclusion

Incidentally encountered IMLNs during microsurgical breast reconstruction are frequently positive. With negligible downside and the possibility to provide additional information for treatment, the procedure should be encouraged. J. Surg. Oncol. © 2016 Wiley Periodicals, Inc.

from Cancer via ola Kala on Inoreader http://ift.tt/1TnWRDf
via IFTTT

Tumor regression grade in gastric cancer: Predictors and impact on outcome

Background

The clinical value and prognostic implications of histologic response to neoadjuvant chemotherapy in gastric cancer is unknown.

Methods

Tumor regression grade (TRG) was recorded in 58 gastric cancer patients identified from two institutional surgical databases. TRG 1a/b represented histologic responders (<10% viable tumor), while TRG 2/3 represented non-responders (>10% viable tumor).

Results

TRG 1a/b was recorded in 10 patients (17%), while 48 patients (83%) had a TRG 2/3 response. Larger tumor size (OR 0.24; 95%CI 0.09, 0.64; P = 0.004) and clinical downstaging (OR 30.0; 95%CI 3.26, 276; P = 0.003) were the only factors predictive of histologic response. TRG 1a/b responders had 3-year survival of 70.0% and an estimated overall survival of >69.8 months compared to 38.2% and 22.8 months in non-responders; however, this trend was not statistically significant (P = 0.535). While TRG could not predict survival (OR 2.40; 95%CI 0.46, 12.57; P = 0.300), patient age (OR 1.06; 95%CI 1.00, 1.11; P = 0.035), and the number of positive lymph nodes (≥7; OR 0.05; 95%CI 0.07, 0.27; P < 0.001) were independent predictors of survival.

Conclusions

Few gastric cancers demonstrate histologic response to neoadjuvant chemotherapy. While TRG may be a valid marker for treatment response, its predictive value and clinical application in gastric cancer remains unclear. J. Surg. Oncol. © 2016 Wiley Periodicals, Inc.

from Cancer via ola Kala on Inoreader http://ift.tt/1YHSoPq
via IFTTT

Assessing the impact of common bile duct resection in the surgical management of gallbladder cancer

Background

Although radical re-resection for gallbladder cancer (GBC) has been advocated, the optimal extent of re-resection remains unknown. The current study aimed to assess the impact of common bile duct (CBD) resection on survival among patients undergoing surgery for GBC.

Methods

Patients undergoing curative-intent surgery for GBC were identified using a multi-institutional cohort of patients. Multivariable Cox-proportional hazards regression was performed to identify risk factors for a poor overall survival (OS).

Results

Among the 449 patients identified, 26.9% underwent a concomitant CBD resection. The median number of lymph nodes harvested did not differ based on CBD resection (CBD, 4 [IQR: 2–9] vs. no CBD, 3 [IQR: 1–7], P = 0.108). While patients who underwent a CBD resection had a worse OS, after adjusting for potential confounders, CBD resection did not impact OS (HR = 1.40, 95%CI 0.87–2.27, P = 0.170). Rather, the presence of advanced disease (T3: HR = 3.11, 95%CI 1.22–7.96, P = 0.018; T4: HR = 7.24, 95%CI 1.70–30.85, P = 0.007) and the presence of disease at the surgical margin (HR = 2.58, 95%CI 1.26–5.31, P = 0.010) were predictive of a worse OS.

Conclusions

CBD resection did not yield a higher lymph node count and was not associated with an improved survival. Routine CBD excision in the re-resection of GBC is unwarranted and should only be performed selectively. J. Surg. Oncol. © 2016 Wiley Periodicals, Inc.

from Cancer via ola Kala on Inoreader http://ift.tt/1sERxVQ
via IFTTT

Lymphocyte to monocyte ratio and prognostic nutritional index predict survival outcomes of hepatitis B virus-associated hepatocellular carcinoma patients after curative hepatectomy

Introduction

Lymphocytes are an integral part of lymphocyte to monocyte ratio (LMR) and prognostic nutritional index (PNI). Both LMR and PNI which reflect body's inflammatory and nutritional status can be obtained from routine blood and biochemical test conveniently. Little evidence concerning the prognostic value of LMR and PNI in hepatocellular carcinoma (HCC) patients has been published. This study aimed to investigate the prognostic value of LMR and PNI in hepatitis B virals (HBV)—associated HCC patients who underwent curative hepatectomy.

Methods

Between January 2008 and June 2013, 450 surgically treated HCC patients were retrospectively analyzed. Clinicopathological parameters, LMR and PNI were collected and compared. The multivariate analysis was performed to indentify independent prognostic factors. Overall survival (OS) and recurrence-free survival (RFS) rates were also compared.

Results

Tumor size, vascular invasion, alpha fetoprotein level, LMR and PNI were independent prognostic factors for OS. Tumor number, tumor size, vascular invasion, LMR and PNI were independent prognostic factors for RFS. Either a high LMR or PNI could predict favorable OS and RFS in surgically treated HCC patients and vice versa.

Conclusions

Both LMR and PNI were significant independent predictors that can predict survival outcomes in HBV-associated HCC patients who received curative hepatectomy. J. Surg. Oncol. © 2016 Wiley Periodicals, Inc.

from Cancer via ola Kala on Inoreader http://ift.tt/1YHSQNH
via IFTTT

Efficacy and Safety of Induction Chemotherapy in Esophageal Cancer with Airway Involvement

Abstract

Purpose

Esophageal cancer with tracheobronchial involvement (TBI) has a poor prognosis. Radical therapy carries the risk of inducing tracheoesophageal fistula (TEF) and treatment-related mortality. Induction chemotherapy followed by reassessment for radical therapy may decrease morbidity and improve outcome.

Methods

This is a retrospective analysis of esophageal cancer patients with TBI who received induction chemotherapy. Airway involvement was defined as bronchoscopic appearance of a bulge into the lumen, restricted or immobile mucosa, frank infiltration, TEF, or stridor, which was clinically due to airway obstruction from the esophageal lesion.

Results

Eighty-three patients were included over 5 years; 97.6 % had squamous histology. All patients received taxane and platinum combination induction chemotherapy; 90.5 % of patients received chemotherapy without dose delays, and 77.8 % patients did not require a dose reduction or modification. The 31.7 % patients had a clinically significant ≥grade 3 toxicity. The objective response rate was 67 % among the patients who underwent restaging scans following induction chemotherapy; 79.5 % of the patients could receive radical intent therapy, either concurrent chemoradiotherapy, or radiation alone, or surgery in one patient. The TEF complication rate was 6 % during the course of therapy. At a median follow-up of 28 months in surviving patients, the estimated median PFS was 8 months (95 % CI 5.5–10.5) and the estimated median OS was 17 months (95 % CI 5.6–28.4). Patients who received radical therapy had a significantly better PFS and OS, p = 0.000.

Conclusions

Induction chemotherapy may improve the outcome of patients with esophageal cancer involving the airway and may help select patients for curative treatment and lower the risk of TEF development.

from Cancer via ola Kala on Inoreader http://ift.tt/1sETi5E
via IFTTT

Combination of carmustine and selenite effectively inhibits tumor growth by targeting androgen receptor, androgen receptor-variants and Akt in preclinical models: New hope for patients with prostate cancer

Abstract

Despite established androgen receptor (AR) antagonists, AR/AR-variants signaling remain a major obstacle for the successful treatment of castration resistant prostate cancer (CRPC). In addition, CRPC cells adapt to survive via AR-independent pathways to escape next generation therapies. Therefore, there is an urgent need for drugs that can target these signaling pathways in CRPC. In the present study, we sought to determine whether carmustine and selenite in combination could induce apoptosis and inhibit growth of CRPC in-vitro and in-vivo. CRPC (22Rv1, VCaP and PC-3) cell culture and xenograft mouse model were used. Combination of carmustine and selenite treatment significantly increased reactive oxygen species, apoptosis and growth inhibition in CRPC cells with down regulation of anti-apoptotic (Bcl-2 and Mcl-1) and proliferative proteins (c-Myc and cyclin-D1). This effect was associated with complete reduction of AR/AR-variants, AR-V7, PSA and significant induction of p27Kip1. Combination treatment substantially abolished phospho-Akt, phospho-GSK-3β and anchorage-independent growth in AR-positive and AR-negative cells. Consistent with in-vitro results, combination treatment effectively induced apoptosis and completely inhibited xenograft tumor growth and markedly reduced AR/AR-variants, AR-V7, PSA, and Bcl-2 in xenograft tumors without causing genotoxicity in host mice. Individual agent treatment showed only partial effect. The combination treatment showed a significant synergistic effect. The present study is the first to demonstrate that the combination of carmustine and selenite treatment completely suppressed CRPC tumor growth by reducing AR/AR-variants and Akt signaling. Our findings suggest that the combination of carmustine and selenite could constitute a promising next-generation therapy for successful treatment of patients with CRPC. This article is protected by copyright. All rights reserved.

from Cancer via ola Kala on Inoreader http://ift.tt/1OCXneI
via IFTTT